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- Title
IL1R1<sup>+</sup> cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer.
- Authors
Koncina, E.; Nurmik, M.; Pozdeev, V. I.; Gilson, C.; Tsenkova, M.; Begaj, R.; Stang, S.; Gaigneaux, A.; Weindorfer, C.; Rodriguez, F.; Schmoetten, M.; Klein, E.; Karta, J.; Atanasova, V. S.; Grzyb, K.; Ullmann, P.; Halder, R.; Hengstschläger, M.; Graas, J.; Augendre, V.
- Abstract
Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC. IL1 signalling pathway has been shown to shape cancer associated fibroblast (CAF) heterogeneity. Here the authors identify a pro-tumorigenic CAF subtype in colorectal cancer characterized by high IL1R1 expression and associated with an immunosuppressive tumor microenvironment.
- Subjects
COLORECTAL cancer; FIBROBLASTS; CANCER cell growth; T helper cells; TUMOR microenvironment; CANCER cell culture
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39953-w